P792: CLINICAL STUDY OF HETROMBOPAG COMBINED WITH CYCLOSPORINE A IN THE TREATMENT OF CHILDREN WITH NON-SEVERE APLASTIC ANEMIA
Authors: Lixian Chang, LI Zhang, Yao Zou, Yumei Chen, Ye Guo, Xiaojuan Chen, Wenyu Yang, Ranran Zhang, Yang Wan, Beibei Zhao, Ruan Min, Xiaoming Liu, Xiaofan Zhu
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Non-severe aplastic anemia (NSAA) is a rare and heterogeneous bone marrow failure disorder characterized by a moderate degree of cytopenia that does not meet the conventional criteria for severe aplastic anemia (AA). There are no standard guidelines for the treatment of NSAA in children. However, due to a large amount of children’s activity, children with platelet counts below 30×109/L have a significantly increased risk of bleeding. New methods to treat these children remain to be explored. Hetrombopag, a TPO receptor agonist made in China, has proven to be effective in treating adult patients with severe AA. Aims: To study the overall efficiency of hetrombopag combined with cyclosporine A （CSA）in the treatment of children with NSAA. Methods: In this study, we analyzed 16 pediatric patients diagnosed with NSAA according to Camitta criteria in China from September 2021 to September 2022. Hetrombopag dosage: 2-5 years old: 0.25 mg/kg/d, 6-11 years old: 7.5 mg/d, over 12 years old: 15 mg QD; CSA: 5-10 mg/kg/d. The results were evaluated as follows: ①Complete response (CR): hemoglobin (HGB) > 100 g/L, platelet count (PLT) > 100×109/L, and neutrophil count (ANC) > 1.5×109/L. ②Good partial response (GPR): independence from the infusion of blood product, HGB > 100 g/L, PLT > 50×109/L, and ANC > 1.0×109/L. ③ Partial therapeutic response (PR): independence from the infusion of blood product, blood routine indexes not reaching the GPR standard. ④No response (NR): no improvement after treatment. Overall response rate = CR + GPR + PR. Results:1) The median age of the 16 patients was 7.5 years (range, 3 to 12 years), with 11 males and 5 females. Of whom, 8 patients were with transfusion-dependent NSAA (TD-NSAA). The median duration of the disease was 3.37 months (range, 0.07 to 86.57 months). The median platelet count was 19×109/L (range, 7 to 42 ×109/L), The median hemoglobin count was 83 g/L (range, 46 to119 g/L), and the median neutrophil count was 0.83×109/L (0.04-2.28). 2) Before treatment with hetrombopag, 3 patients were treated with CSA, 2 patients were treated with traditional Chinese medicine, 5 patients were treated with CSA combined with Chinese medicine, and 6 patients were observed. 3) After 3 months of treatment with hetrombopag and CSA, 15 patients were followed up, and the overall response rate was 73.3% (11/15). Effective median platelet count and hemoglobin level were 35 × 109/L (range, 22 to 108 × 109/L) and 92 g/L (range, 52 to 129 g/L). The median number of neutrophils was 1×109/L (range, 0.59 to 2.85 ×109/L). After 6 months, 15 patients were followed up, and the overall response rate was 66.7% (10/15). Effective median platelet count and hemoglobin level were 50×109/L (range, 23 to 112 ×109/L) and 104.5 g/L (range, 72 to 135 g/L). The median number of neutrophils was 1.56×109/L (range, 0.67 to 3.4/L). Platelets, hemoglobin, and neutrophils increased significantly after treatment with hetrombopag, as shown in Figure 1. 4) After 6 months of treatment with hetrombopag, 7 of the 8 TD-NSAA patients were followed up, and 5 patients were free from blood transfusions. The overall response rate was 71.4%. Summary/Conclusion: Hetrombopag combined with CSA can treat non-severe aplastic anemia in children. Hetrombopag is effective in TD-NSAA patients.Figure 1. The increasing trend of platelet, neutrophil, and hemoglobin Keywords: Aplastic anemia, Cyclosporin A, Thrombopoietin (TPO)